CORONARY AND AORTIC VASCULAR RESPONSIVENESS TO ENDOTHELIN IN THE GUINEA PIG.
Contributors: University of Michigan.
Published: 1989
Number of pages: 85
Subjects: Health Sciences, Nursing.
Description: Endothelin, an endothelium-derived vasoactive peptide, has potent constrictor properties. This work examines changes in vascular reactivity to endothelin in hearts perfused with buffer (modified Langendorff technique) in 3 groups of guinea pigs: normal salt normotensive, high salt normotensive, and deoxycorticosterone acetate (DOCA) salt hypertensive. For comparison, force generation in aortic rings was measured. In normal salt normotensive animals, endothelin induced dilation in both the coronary vasculature and aorta. Endothelium damage or removal converted dilation to endothelin to constriction in the coronary vasculature and aorta, whereas indomethacin pretreatment blunted the dilation in the coronary vasculature only. Maximal coronary constrictor responses to endothelin were not altered by endothelium damage, whereas maximal aortic constrictor responses to endothelin were increased after endothelium removal. Further, the threshold dose of endothelin which increased perfusion pressure 10 mmHg was about 100 fold lower for endothelin than for prostaglandin F$\sb2□\alpha.□$ In all 3 groups, calcium-free medium blunted coronary and aortic constrictor responses, and readdition of calcium restored responses. In all 3 groups, nifedipine, a calcium channel blocker, inhibited about half of the coronary constriction to endothelin (10$\sp-□9 □$moles). In the 2 high salt groups, coronary dilation to endothelin was not observed, and constrictor sensitivity to endothelin was enhanced compared to the normal salt group. In hypertensive animals, maximal constrictor responses to endothelin were augmented. In the hypertensive group only, coronary vascular resistance was not reduced in response to acetylcholine or adenosine triphosphate, endothelium-dependent dilators.

We conclude that in normal salt normotensive animals endothelin has dilator and constrictor properties. Endothelin is a more potent coronary constrictor than prostaglandin F$\sb2□\alpha.□$ Additionally, coronary dilation to endothelin requires an intact endothelium, and occurs through a prostaglandin-mediated mechanism. Coronary constriction is not mediated through the release of a factor from the endothelium. Endothelin-induced aortic dilation and attenuation of endothelin-induced aortic constriction are mediated through the release of a factor from the endothelium. In all 3 groups, endothelin-induced coronary and aortic constriction require extracellular calcium; in part entering through nifedipine-sensitive channels. Increased sensitivity to endothelin in DOCA-treated guinea pigs is related to salt intake. In mineralocorticoid hypertension, endothelium-dependent dilator capacity is reduced.
Notes: Source: Dissertation Abstracts International, Volume: 51-01, Section: B, page: 0143.

Thesis (PH.D.)--THE UNIVERSITY OF MICHIGAN, 1989.

School code: 0127.